The interactions between an exchangeable mimic of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), Phos(+/-), with an exchangeable mimic of cholesterol, Chol, have been analyzed in fluid bilayers by means of nearest-neighbor recognition measurements. These interactions have been found to be very similar to those of an exchangeable mimic of 1,2-dipalmitoyl-sn-glycerol-3-phospho-(1'rac-glycerol) (DPPG), Phos(-), interacting with Chol. Thus, both phospholipids have a similar preference for becoming nearest-neighbors of Chol in the liquid-ordered (l(0)) phase, and both mix, ideally, with Chol in the liquid-disordered (l(d)) phase. These findings, together with the almost negligible screening effects found for the latter, provide strong evidence that electrostatic forces play a minor role in the preference that both phospholipids have in becoming a favored nearest-neighbor of Chol. They also imply that the main driving force for forming the liquid-ordered phase, and for defining the lateral organization of this phase, is an intrinsic affinity that high-melting lipids and cholesterol have for each other.